Sir, Aspergillus fumigatus may cause allergic bronchopulmonary aspergillosis (ABPA), aspergillomas or Aspergillus bronchitis in patients with cystic fibrosis (CF). Oral corticosteroids provide the mainstay of treatment for ABPA, but there are concerns about the side effects of long-term corticosteroid use. Itraconazole has been used as a steroid-sparing agent, but absorption in people with CF is poor and unreliable. Voriconazole, a broadspectrum triazole antifungal agent, may be useful for the management of fungal infections in people with CF. We undertook an open-label Phase IV pharmacokinetic study, which aimed to recruit 10 adults with CF, hospitalized for routine antibiotic therapy and with pancreatic insufficiency. Each subject received 400 mg of oral voriconazole (VFEND, Pfizer) 12 hourly on day 1, followed by 200 mg 12 hourly for the subsequent 13 days of the study. Venous blood samples were obtained for drug analysis pre-dose and at 1, 2, 4, 6, 8 and 12 h post-dose on days 1 and 14 of the study. Serum voriconazole levels were determined using liquid chromatography–tandem mass spectrometry. On days 1, 7 and 14, routine haematology, liver function tests and blood chemistry samples were taken. All suspected unexpected serious adverse reactions and serious adverse events were recorded. Data were expressed as the mean and standard deviation (SD). The maximum concentration (Cmax) and the time of maximum concentration (Tmax) were determined by visual inspection of the data. The area under the plasma concentration–time curve during the dosing interval (AUC0 – 12) was determined using trapezoidal summation. Determination of the elimination constant (kel) and half-life (t12) were undertaken using least squares non-linear regression of the experimental data (GraphPad Prism 5.02, GraphPad Inc., USA). The clearance for the fraction of drug absorbed (CL/F) for voriconazole was calculated as the dose/AUC0 – 12 ratio. The volume of distribution for the fraction of drug absorbed (V/F) was estimated as dose/(kel .AUC0 – 12). This study was approved by the Leeds (East) Research Ethics Committee. Regulatory approval was obtained from the UK Medicines and Healthcare products Regulatory Agency. Informed written consent was obtained from all subjects. Data were available from nine patients (seven males and two females). The study subjects had a mean percentage predicted forced expiratory volume in 1 s (FEV1%) (SD), percentage predicted forced vital capacity (FVC%) (SD) and weight (SD) of 38.7% (16.3%), 50.7% (17.1%) and 53.6 kg (7.1 kg), respectively. On day 1, the Cmax (SD) was 3.8 mg/L (1.6 mg/L) and occurred at 2.3 h (1.2 h). At the end of the study, the Cmax was 2.7 mg/L (0.8 mg/L) and occurred at 2.3 h (1.3 h) (see Figure 1). At day 14, all subjects achieved a peak serum voriconazole level of .1.0 mg/L and a trough level of .0.25 mg/L. The AUC0 – 12 (SD) was 24.0 h.mg/L (16.2 h.mg/L) and 15.5 h.mg/L (8.1 h.mg/L) on days 1 and 14, respectively. On days 1 and 14, the t1 2 (SD) for oral voriconazole was 8.0 h (5.8 h) and 5.4 h (3.4 h), respectively. The V/F (SD) was 200.8 L (82.1 L) and 100.3 L (48.2 L) on days 1 and 14, respectively. The CL/F (SD) was 26.2 L/h (19.0 L/h) and 14.9 L/h (8.2 L/h) on days 1 and 14, respectively. Three subjects withdrew due to side effects; two subjects due to visual disturbance on days 1 and 3 (both had peak levels .5 mg/L), and one on day 7 due to liver function test derangement. All symptoms resolved on cessation of voriconazole. Purkins et al. reported the V/F and CL/F for 200 mg of voriconazole orally to be 160.2 L and 19.9 L/h, respectively. The data from the present study would suggest that voriconazole has a higher volume of distribution, but slower clearance in patients with CF. Patients with CF are almost always pancreatic insufficient, resulting in poor absorption from the gastrointestinal tract, and may have an increased volume of distribution and faster drug clearance. Berge et al. documented 14% and 30% of patients with CF developed neurological and hepatic